DNA-coated gold nanoparticles for sensing and drug delivery

DNA-coated gold nanoparticles for sensing and drug delivery

DNA-coated gold nanoparticles for sensing and drug delivery

In recent years inorganic nanoparticles have been of great scientific interest not only due to the fact that they can be tailored in morphology allowing for the tuning of their optical and electronic properties but also due to their rich surface chemistry. Recent advances in conjugation techniques have allowed for the surface functionalization of nanoparticles with ligands such as synthetic oligonucleotides. This has led to the development of bio-nanomaterials that have been successfully used in applications ranging from bio sensing to the targeted delivery of molecules such as drugs.

This thesis focuses on the design and synthesis of advanced DNA-coated gold nanostructures that can perform the synergistic tasks of sensing and drug delivery in cells.

Gold nanoparticles functionalized with synthetic oligonucleotides were assembled into dimers using copper free click chemistry and were used for the intracellular detection of up to two mRNA targets. Once taken up by cells they showed great biocompatibility, no significant susceptibility to degradation by nucleases and most importantly excellent specificity towards the mRNA sequence they were designed to detect.

Furthermore, DNA-coated gold nanoparticle dimers were developed into multifunctional nanostructures. In addition to live cell mRNA detection we showed how they could also be designed to deliver up to two chemotherapeutic drugs. By relying on the specificity of the gold nanoparticle dimer towards an mRNA target, cell specific drug delivery was made possible thus demonstrating the synergistic capabilities of this system.

Finally with a view of shedding light on the interaction between DNA-coated gold nanoparticles and cells their intracellular fate including the time point and location of mRNA detection after cellular entry was investigated.

Abstract

In recent years inorganic nanoparticles have been of great scientific interest not only due to the fact that they can be tailored in morphology allowing for the tuning of their optical and electronic properties but also due to their rich surface chemistry. Recent advances in conjugation techniques have allowed for the surface functionalization of nanoparticles with ligands such as synthetic oligonucleotides. This has led to the development of bio-nanomaterials that have been successfully used in applications ranging from bio sensing to the targeted delivery of molecules such as drugs.

This thesis focuses on the design and synthesis of advanced DNA-coated gold nanostructures that can perform the synergistic tasks of sensing and drug delivery in cells.

Gold nanoparticles functionalized with synthetic oligonucleotides were assembled into dimers using copper free click chemistry and were used for the intracellular detection of up to two mRNA targets. Once taken up by cells they showed great biocompatibility, no significant susceptibility to degradation by nucleases and most importantly excellent specificity towards the mRNA sequence they were designed to detect.

Furthermore, DNA-coated gold nanoparticle dimers were developed into multifunctional nanostructures. In addition to live cell mRNA detection we showed how they could also be designed to deliver up to two chemotherapeutic drugs. By relying on the specificity of the gold nanoparticle dimer towards an mRNA target, cell specific drug delivery was made possible thus demonstrating the synergistic capabilities of this system.

Finally with a view of shedding light on the interaction between DNA-coated gold nanoparticles and cells their intracellular fate including the time point and location of mRNA detection after cellular entry was investigated.